1.Research progress on the characteristics of γδ T cells in breast cancer patients and their anti-breast cancer mechanism
Renhong ZHU ; Shicai ZHANG ; Keqiang WANG
International Journal of Biomedical Engineering 2025;48(5):489-500
γδ T cells are a distinct subset of T lymphocytes that demonstrate anti-tumor activity that is not contingent upon conventional major histocompatibility complex-restricted antigen presentation. These cells demonstrate extensive reactivity to anti-breast cancer cells and are capable of exerting anti-breast cancer through mechanisms such as direct cell killing and immune regulation. γδ T cells are a promising type of effector cell that is being developed for the treatment of breast cancer through immunotherapy. Immunotherapy has emerged as a critical treatment modality for patients with postoperative or advanced breast cancer. The activation of γδ T cells in vivo or their use in adoptive cell therapy has emerged as a potential strategy for breast cancer immunotherapy. In this review, research progress on the characteristics of γδ T cells in breast cancer patients and their anti-breast cancer mechanism were summarized.
2.Prospective analysis of autophagy in prostate cancer cells based on gene expression databases and investigation of the C-Met regulatory mechanism
Ru ZHANG ; Yongqiang XIE ; Qiang ZHAO ; Keqiang CHAI ; Yulin LIU
Immunological Journal 2025;41(10):750-761
Objective To investigate the prognostic value of mitochondrial autophagy-related genes(MRGs)in prostate cancer(PCa),and to reveal their regulatory relationship with interstitial epidermal transforming factor(C-Met)based on the Gene Expression Database(GEO).Methods Single-cell RNA sequencing(scRNA-seq)data of three PCa samples were obtained from the GSE153892 dataset of GEO,and MRGs were collected from the Genecards database and previous literature.The scRNA-seq data were processed and analyzed using the Seurat software package,including quality control,gene expression screening,cell type annotation,differentially expressed genes(DEGs)identification,and intersection analysis with MRGs.The transcriptome data of PCa and control samples were downloaded from the Cancer Genome Atlas Database(TCGA)-PRAD cohort,and differential expression analysis and copy number variation analysis were conducted.The non-negative matrix factorization algorithm is adopted to conduct cluster analysis on PCa samples to identify different PCa subtypes.A prognostic risk model based on intersection genes was constructed,and the predictive ability of the model was analyzed through Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic(ROC)curve analysis.Conduct independent prognostic analysis,construct a nomogram model based on risk scores and clinical characteristics,and evaluate its ability to predict patient survival rates.The possibility of immune infiltration and tumor immune escape in PCa samples was evaluated by using the single-sample Gene Set Enrichment analysis(ssGSEA)algorithm and the TIDE database.The relationship between intersection genes and C-Met expression was analyzed using Pearson correlation analysis.Results scRNA-seq data analysis identified five cell types including B lymphocytes,epithelial cells,monocytes,natural killer cells and T lymphocytes,and discovered the intersection genes that were highly expressed in different cell types.Through differential expression analysis,genes significantly related to the prognosis of PCa patients were screened out,and a prognostic risk model was constructed.Six genes such as ADH5 and CAT were retained through LASSO analysis.A diagnostic model was constructed and grouped.There was a significant difference in survival time between the two groups in the internal test set(P<0.05).ROC curve evaluation showed that the model had a good predictive ability for 1-,3-,and 5-year survival rates.The external test set verified that there was a statistically significant difference in the expression of intersection genes(P<0.05).Independent prognostic analysis identified T stage and risk score as independent prognostic factors.A nomogram model was constructed.Calibration curve and ROC curve analyses showed that the predictive ability of this model was superior to that of the simple risk model.ssGSEA analysis revealed differences in the abundance of immune cell inflammation and immune function scores between the two groups.Most immune cells,immune function,and risk scores were related to the modeling genes.There were significant differences in TIDE scores and multiple immune checkpoints between the high-risk and low-risk groups(P<0.05).BCAT2,DCXR,OGT and FUS were positively correlated with the expression of C-Met,while ADH5 and CAT were negatively correlated with the expression of C-Met(P<0.05).Conclusion The prognostic risk model based on intersection genes can effectively predict the prognosis of patients with PCa,and the risk score and T stage are independent prognostic factors for PCa.The correlation analysis of intersection genes and C-Met expression provides a new idea for the targeted therapy of PCa.
3.Performance Optimization of Biomimetic Flexible Actuators Driven by Multidimensional Structure-Function Coupling Mechanism of Skeletal Muscles
Fan ZHANG ; Jie SHEN ; Guanwu JIANG ; Keqiang BAI ; Tao LI
Journal of Medical Biomechanics 2025;40(5):1186-1192
Objective The biological characteristics and action mechanisms underlying the excellent performance of skeletal muscles were studied through experiments to provide a scientific basis for the development of flexible actuators with performance comparable to that of skeletal muscles.Methods A frog skeletal muscle sample was contracted by applying electrical stimulation,and then tensile load was applied to it to analyze the relationship between the driving properties(such as contraction length and output force)of skeletal muscle and its structure from three aspects:skeletal muscle dimensions,tendon,and epimysium.Results The contraction lengths of these skeletal muscle samples were approximately 28.92%and 20%under unloaded conditions and under 50%of their maximum output force,respectively.When the load on the skeletal muscles did not exceed 20%of their maximum output force,they also exhibited the property of rapid reduction(approximately 1.25 s).The active tendon increased contraction by approximately 19.68%compared with the inactive tendon,and the integrity of the epimysium protected the force transfer efficiency of skeletal muscles.Conclusions By simulating the structural and biomechanical properties of skeletal muscles,flexible actuators can achieve better driving performance,thus greatly promoting the development of bionic robots.
4.Performance Optimization of Biomimetic Flexible Actuators Driven by Multidimensional Structure-Function Coupling Mechanism of Skeletal Muscles
Fan ZHANG ; Jie SHEN ; Guanwu JIANG ; Keqiang BAI ; Tao LI
Journal of Medical Biomechanics 2025;40(5):1186-1192
Objective The biological characteristics and action mechanisms underlying the excellent performance of skeletal muscles were studied through experiments to provide a scientific basis for the development of flexible actuators with performance comparable to that of skeletal muscles.Methods A frog skeletal muscle sample was contracted by applying electrical stimulation,and then tensile load was applied to it to analyze the relationship between the driving properties(such as contraction length and output force)of skeletal muscle and its structure from three aspects:skeletal muscle dimensions,tendon,and epimysium.Results The contraction lengths of these skeletal muscle samples were approximately 28.92%and 20%under unloaded conditions and under 50%of their maximum output force,respectively.When the load on the skeletal muscles did not exceed 20%of their maximum output force,they also exhibited the property of rapid reduction(approximately 1.25 s).The active tendon increased contraction by approximately 19.68%compared with the inactive tendon,and the integrity of the epimysium protected the force transfer efficiency of skeletal muscles.Conclusions By simulating the structural and biomechanical properties of skeletal muscles,flexible actuators can achieve better driving performance,thus greatly promoting the development of bionic robots.
5.Prospective analysis of autophagy in prostate cancer cells based on gene expression databases and investigation of the C-Met regulatory mechanism
Ru ZHANG ; Yongqiang XIE ; Qiang ZHAO ; Keqiang CHAI ; Yulin LIU
Immunological Journal 2025;41(10):750-761
Objective To investigate the prognostic value of mitochondrial autophagy-related genes(MRGs)in prostate cancer(PCa),and to reveal their regulatory relationship with interstitial epidermal transforming factor(C-Met)based on the Gene Expression Database(GEO).Methods Single-cell RNA sequencing(scRNA-seq)data of three PCa samples were obtained from the GSE153892 dataset of GEO,and MRGs were collected from the Genecards database and previous literature.The scRNA-seq data were processed and analyzed using the Seurat software package,including quality control,gene expression screening,cell type annotation,differentially expressed genes(DEGs)identification,and intersection analysis with MRGs.The transcriptome data of PCa and control samples were downloaded from the Cancer Genome Atlas Database(TCGA)-PRAD cohort,and differential expression analysis and copy number variation analysis were conducted.The non-negative matrix factorization algorithm is adopted to conduct cluster analysis on PCa samples to identify different PCa subtypes.A prognostic risk model based on intersection genes was constructed,and the predictive ability of the model was analyzed through Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic(ROC)curve analysis.Conduct independent prognostic analysis,construct a nomogram model based on risk scores and clinical characteristics,and evaluate its ability to predict patient survival rates.The possibility of immune infiltration and tumor immune escape in PCa samples was evaluated by using the single-sample Gene Set Enrichment analysis(ssGSEA)algorithm and the TIDE database.The relationship between intersection genes and C-Met expression was analyzed using Pearson correlation analysis.Results scRNA-seq data analysis identified five cell types including B lymphocytes,epithelial cells,monocytes,natural killer cells and T lymphocytes,and discovered the intersection genes that were highly expressed in different cell types.Through differential expression analysis,genes significantly related to the prognosis of PCa patients were screened out,and a prognostic risk model was constructed.Six genes such as ADH5 and CAT were retained through LASSO analysis.A diagnostic model was constructed and grouped.There was a significant difference in survival time between the two groups in the internal test set(P<0.05).ROC curve evaluation showed that the model had a good predictive ability for 1-,3-,and 5-year survival rates.The external test set verified that there was a statistically significant difference in the expression of intersection genes(P<0.05).Independent prognostic analysis identified T stage and risk score as independent prognostic factors.A nomogram model was constructed.Calibration curve and ROC curve analyses showed that the predictive ability of this model was superior to that of the simple risk model.ssGSEA analysis revealed differences in the abundance of immune cell inflammation and immune function scores between the two groups.Most immune cells,immune function,and risk scores were related to the modeling genes.There were significant differences in TIDE scores and multiple immune checkpoints between the high-risk and low-risk groups(P<0.05).BCAT2,DCXR,OGT and FUS were positively correlated with the expression of C-Met,while ADH5 and CAT were negatively correlated with the expression of C-Met(P<0.05).Conclusion The prognostic risk model based on intersection genes can effectively predict the prognosis of patients with PCa,and the risk score and T stage are independent prognostic factors for PCa.The correlation analysis of intersection genes and C-Met expression provides a new idea for the targeted therapy of PCa.
6.Projection domain and image domain joint learning reconstruction network for reconstructing chest limited angle CT images
Jie CHEN ; Keqiang WANG ; Jianbo JIAN ; Peng WANG ; Jun WU ; Wenxue ZHANG
Chinese Journal of Medical Imaging Technology 2024;40(9):1410-1416
Objective To observe the value of dual domain(projection domain and image domain)joint learning reconstruction network(DDRNet)for reconstructing chest limited angle CT images.Methods Totally 4 300 chest enhanced CT images of 65 patients with chest tumors were retrospectively enrolled and reconstructed with DDRNet,and 3D and 2D projection information fusion were performed.The reconstruction effect of DDRNet was evaluated and compared with that of single domain reconstruction and filtered back projection(FBP),residual encoder-decoder convolutional neural network(RED-CNN),Resnet and deconvolution network(RDN),as well as of generative adversarial network(GAN).Results The peak signal to noise ratio(PSNR)of DDRNet reconstructed images tended to stabilize after approximately 60 iterations,while the projection domain and image domain learning networks tended to stabilize after approximately 90 and 80 iterations.After stable training,compared to the projection domain learning network,the fluctuation of output results of DDRNet and image domain learning networks were less.After 200 rounds of training,PSNR of DDRNet reconstructed images was significantly higher than that of projection domain and image domain learning networks.The quality of DDRNet reconstructed image was significantly better than that of FBP,RED-CNN,RDN and GAN.Conclusion DDRNet could be used to effectively reconstruct high-quality chest limited angle CT images.
7.Impact of tumor treating fields transducer arrays on concurrent radiotherapy dosimetry
Keqiang WANG ; Jie CHEN ; Jianbo JIAN ; Peng WANG ; Xinshan ZHANG ; Hongyang ZHANG ; Wenxue ZHANG
Chinese Journal of Radiation Oncology 2024;33(5):438-445
Objective:To investigate the dosimetric impact of tumor treating fields (TTF) transducer arrays on concurrent radiotherapy for patients with glioblastoma (GBM).Methods:A strategy was developed to accurately simulate the dosimetric impact of TTF arrays on radiotherapy, including the establishment of accurate auto-segmentation technique for TTF arrays, determination of the relative electron density (RED) of the transducer arrays and validation of the dose calculation accuracy in the treatment planning system (TPS) for TTF arrays. Based on this strategy, the dosimetric impact of TTF arrays on clinical treatment plans of 10 patients with GBM was evaluated. Furthermore, the dosimetric comparison between the clinical plans with different beam energies were investigated when TTF arrays were used. The methods of analysis of variance were paired t-test or Wilcoxon signed-rank test based on whether the differences followed a normal distribution. Results:The auto-segmentation technique for TTF arrays was established by designing a workflow in Mim software and achieved a Dice coefficient of 0.93 and a Jaccard index of 0.87 compared to the standard contours. The RED of TTF arrays was 3.3 which was derived from the comparison between the measured and simulated percentage depth dose (PDD) with and without TTF arrays on phantom. Measured and calculated dose distributions were compared using the 2D gamma analysis. The gamma passing rates on the coronal plane of 4 mm and 5.1 cm depth were 96.64% and 94.55% at the criteria of 3% /3 mm, indicating that the calculation accuracy of algorithm in TPS for TTF arrays could meet clinical requirements. In the clinical treatment plans of patients with GBM, the presence of TTF arrays caused a mean reduction of planning target volume (PTV) dose of approximately 1%, and an increase in scalp dose of approximately 5%, with minimal impact on other organs at risk (OAR). The 10 MV plans resulted in a higher dose of PTV by 0.3% and lower dose of scalp by approximately 3% compared to the 6 MV plans, when considering TTF arrays.Conclusions:The accurate simulation strategy for the dosimetric impact of TTF arrays on radiotherapy established in this study ensures the accuracy and precision of the calculations. In TTF therapy combined with concurrent radiotherapy for GBM, TTF arrays have slight effect on PTV dose, but significantly increase scalp dose. High-energy beam can reduce the impact of TTF arrays.
8.Plan quality comparison between coplanar and non-coplanar VMAT for the whole brain radiotherapy with hippocampus and hypothalamic-pituitary axis sparing
Keqiang WANG ; Jie CHEN ; Jianbo JIAN ; Peng WANG ; Xinshan ZHANG ; Hongyang ZHANG ; Wenxue ZHANG
Chinese Journal of Radiation Oncology 2024;33(7):634-641
Objective:To compare the plan quality between coplanar and non-coplanar volumetric modulated arc therapy (co-VMAT and nco-VMAT) techniques for the whole brain radiotherapy with hippocampus and hypothalamic-pituitary (HT-P) axis sparing.Methods:A total of 15 patients who underwent prophylactic cranial irradiation in Tianjin Medical University General Hospital from November 2021 to August 2023 were retrospectively selected. The hippocampus and HT-P axis were delineated according to Radiation Therapy Oncology Group (RTOG) 0933 and contouring guidelines for hypothalamus. Co-VMAT and nco-VMAT plans were generated for each patient with a prescription dose of 30 Gy in 10 fractions. Then, dosimetric parameters, plan robustness, plan complexity, and delivery efficiency for both plans were compared using paired t-test. Results:Both co-VMAT and nco-VMAT plans could achieve dosimetric objectives. There were no significant differences in D 2%, D 95% and conformity index (CI) of planning target volume (PTV) between the two plans. The D 98% and homogeneity index (HI) of PTV in co-VMAT showed a slight inferiority compared to that in nco-VMAT (D 98%: 26.37 Gy vs. 26.96 Gy, P=0.001; HI: 0.25 vs. 0.24, P=0.002). The D min of bilateral hippocampus in co-VMAT were 8.55 Gy (left) and 8.32 Gy (right), which were lower than 9.31 Gy (left) and 9.26 Gy (right) in nco-VMAT. In addition, the D mean of the hypothalamus and pituitary in the co-VMAT plan were lower than those in the nco-VMAT plan (hypothalamus: 11.54 Gy vs. 12.27 Gy; pituitary: 11.72 Gy vs.12.1 Gy, both P<0.001). The doses to the hippocampus and HT-P axis were highly sensitive to errors in both co-VMAT and nco-VMAT plans, while the sensitivity of dose to errors in the PTV and other organs at risk was low. The co-VMAT plan had lower complexity compared to the nco-VMAT plan, with γ passing rate at 3%/3 mm criteria of 99.06%±0.60% and 98.05%±2.89%, respectively. The average beam-on time of the co-VMAT plan was 4.8 min, approximately 2/3 of the time for nco-VMAT, while the average treatment time was 6.3 min, approximately half of the treatment time for nco-VMAT. Conclusions:Both co-VMAT and nco-VMAT can achieve hippocampus and HT-P axis sparing in the whole brain radiotherapy. In the co-VMAT plan, the D 98% of the PTV is slightly smaller, but it provides better protection for the hippocampus and HT-P axis. The doses to the hippocampus and HT-P axis are sensitive to errors in both plans. However, the co-VMAT plan has lower complexity, higher delivery efficiency, and is more suitable for clinical treatment.
9.Endovascular therapy combined with laparoscopic surgery for acute mesentery artery occlusion
Keqiang ZHAO ; Peng ZHANG ; Junlai ZHAO ; Tong ZHANG ; Zhanjiang CAO ; Yu YANG ; Chao JIANG ; Rongrong ZHU ; Weiwei WU
Chinese Journal of General Surgery 2024;39(3):192-196
Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.
10.Comparative study of different radiotherapy schemes for NSCLC based on radiobiological model
Peng WANG ; Jie CHEN ; Keqiang WANG ; Wenxue ZHANG
China Medical Equipment 2024;21(12):32-38
Objective:To compare the difference of tumor control probability (TCP) and normal tissue complication probability (NTCP) between different radiotherapy schemes bases on biological model of non-small cell lung cancer(NSCLC) that used in assessing radiotherapy. Methods:The radiotherapy data of 15 NSCLC patients who admitted to Tianjin Medical University General Hospital from April 2021 to July 2022 were collected. The low resolution Poisson (TCP Poisson LQ) model,Zaider Minerbo (TCP-ZM) model and TCP Logit model were respectively adopted to fit TCP curve for all patients. Lyman-Kutcher-Burman (LKB) model and linear quadratic (LQ) model were adopted to fit NTCP curves for comparing applicability of several models in tumor control rate,radiation pneumonitis and radiation pericarditis,and the differences in TCP and NTCP among conventional radiotherapy regimen (scheme 1),regimen of maximum gain ratio of treatment (scheme 2),and maximum segmentation frequency regimen (scheme 3) as mean lung dose (MLD)<20 Gy. Results:The average TCP of the TCP Poisson LQ model was (87.2±11.92)% at 60-70 Gy,which met the requirement of clinical dose. The incidence rate of radiation pneumonitis,which was calculated by the NTCP-LQ model,was higher than that by the NTCP-LKB model when the average radiation dose of whole lung was less than 26 Gy. In the comparison of different schemes,the TCP mean of scheme 3 was (81.56±11.20)%,which was respectively higher than that of other two schemes (60.28±8.04)% and (69.46±18.09)%,and the differences of them were statistically significant (t=-6.196,-1.969,P<0.05). The average incidence of radiation pneumonitis in Scheme 3 was (19.24±0.43)%,which was respectively higher than that in Scheme 1 and Scheme 2[(15.07±3.24)% and (15.89±4.55)%],respectively,and the differences of them were statistically significant (t=-5.878,-2.386,P<0.05). Conclusion:It is reasonable to use Poisson-LQ model and NTCP-LQ model to calculate TCP,and incidence of radiation pneumonitis in NSCLC patients. The maximum segmentation frequency scheme (Scheme 3) can effectively improve TCP under the premise of ensuring treatment safety when MLD<20 Gy.

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